PL178167B1 - Method of obtaining dissymmetrically substituted triazines - Google Patents

Abstract

PCT No. PCT/EP94/03331 Sec. 371 Date Mar. 29, 1996 Sec. 102(e) Date Mar. 29, 1996 PCT Filed Oct. 10, 1994 PCT Pub. No. WO95/11237 PCT Pub. Date Apr. 27, 1995A process for preparing asymmetrically substituted triazines of the formula I <IMAGE> I where R1 is hydrogen, methyl or ethyl, R2 and R3 independently of one another are an unsubstituted or substituted hydrocarbon radical, by reaction of a cyanoguanidine of the formula II <IMAGE> II with a carboxylic acid derivative in the presence of an alcohol of the formula III R2-OHIII,which comprises reacting a carboxylic acid ester of the formula IV R3-COOR4IV,where R3 has the abovementioned meaning and R4 is an unsubstituted or substituted hydrocarbon radical, in the presence of a base or of a carboxamide selected from the group consisting of N,N-dialkylformamide, N,N-dialkylacetamide and N-methylpyrrolidone and in the presence of a salt or of a salt-like compound of the elements magnesium, calcium, aluminum, zinc, copper, iron, cobalt, nickel or chromium, is described.

Description

The present invention relates to a process for the preparation of triazine derivatives which are unsymmetrically substituted.

Such triazine derivatives can be prepared by various methods, e.g. starting from N-cyanamides, by reaction of Vilsmeier complexes (RLN Harries, Aust. J. Chem. 34 (1981) 623), N-cyanoimidic acid esters ( DE-A 34 11 202; MA Perez, JL Soto, Heterocycles, 20 (1983) 463; KR Huffman, FC Schaefer, J. Org. Chem. 28 (1983) 1816) or bisguanidines (SL Shapiro et al., J. Org. Chem. 25 (1960) 379; US-A 2,535,968). The reaction of amidine thiourea with dimethyl sulfate and carboxylic acid derivatives is also known (H. Eilingsfeld, H. Scheuermann, Chem. Ber. 100 (1967) 1874; DE-A 16 70 147; EP-A 545 149) and the reaction of trichloroacetamidine guanidines with acid derivatives trifluoroacetic acid (DE-A 40 34 078). According to these methods, the reactions are carried out without the formation of chelate complexes as intermediates.

6-Trifluoromethyl-1,3,5-triazines can be prepared by the method given in Yakugaku Zasshi 95, 499-511 (1975), in which N-cyanoguanidines are converted to copper complexes with N-amidine-O-alkylisoureas, urea derivatives are released by treatment with hydrogen sulfide and then reacted with a trifluoroacetic acid ester according to the following reaction scheme:

N NH

HI Η + R0H

NIT, + 1/2 CuCl ₂ i

H.

NH NH I! II _x C _xz c _x 1/2 Cuci, R-0 N NH,

H.

NH NH +1/2 ELS CC

- 1/2 CuS ^R -OYM

H.

HCl

NaOR

CF ₃ COOR

R-0

On

DD-A-252 374 discloses a variant of this process in which copper acetate is used instead of copper (II) chloride.

In this process, a stoichiometric amount of copper salt is needed; without copper, instead of N-amidino-O-alkylisourea, mainly amidineurea is formed (Kyushu Kogyo Daigaku HokokuNo. 12, 69-78 (1962).

178 167

The reaction of N-amidino-O-alkylisourea hydrochloride with ethyl chloroacetate in an ethanol / NaOC2H5 mixture leads to the corresponding chloromethyltriazine obtained in low yield. The starting material should be freed from the copper complex beforehand.

The method of producing chelate complexes by reacting cyanoguanidine with copper acetate or zinc chloride in methanol is described by R.I. Dutta and A: Syamal in Coord. Chem. Rev., vol. 2, 1967, pp. 441-457. Chemistry of Heterocyclic.Compounds, Vol. 25, 1989, p. 547550 describes the isolation of such zinc complexes and reacting them with trifluoroacetic anhydride to form a triazine.

In a similar way, zinc sulphate forms a chelate complex which, after boiling in water, decomposes in a second reaction step into amidine-O-methylisourea sulphate (US-A 3 360 534, IN-A 167 500) which in the the third step can be reacted with acetic anhydride (S. Lotz, G. Kiel, G. Gattow, Z. Anorg. Allg. Chem. 604 (1991) 53-62) or with trifluoroacetate. methyl, (T. Tsujikawa. Yakugaku Zasshi 95, supra) to give the triazine in a yield of 31. or 26%.

Such multistage processes are costly and, in the case of esters, lead to the desired triazines in a low yield, and in the case of anhydrides, stoichiometric amounts of carboxylic acids are produced, which can only be recycled to the corresponding anhydrides with very high expenditure. Typically, heavy metal complexes, which are toxicologically harmful and sometimes difficult to separate by filtration, have to be isolated, and then reacted with anhydrides in an inert solvent because an alcoholic solution cannot be used due to the reaction of the anhydrides with alcohols. In addition, the described processes are disadvantageous in that relatively large amounts of heavy metal salts are obtained in the form of organic sludges, which can hardly be removed.

US-A 4,886,881 describes a one-step synthesis of 2-aminotriazines in which cyanoguanidine is reacted with trimethyl orthoacetate in the presence of a Lewis acid such as zinc chloride as a catalyst. Dimethylformamide and acetyl nitrile are preferred as a solvent.

The object of the invention was to provide a process for the preparation of triazine derivatives by reacting cyanoguanidines with carboxylic acid esters, which are more readily available, although less reactive than the corresponding anhydrides or orthoesters. This process should be capable of carrying out the reaction without isolation of intermediates (one-pot reaction). A method has now been developed to meet these requirements.

Thus, a new process for the preparation of triazine derivatives of the general formula 1 R ³

N ^ N

HN

OR ² wherein R ¹ is hydrogen, methyl or ethyl, R ² is C 1 -C, t-alkyl and R ³ is C 1 -C 6 -alkyl optionally substituted with one or more chlorine or fluorine atoms by reaction of the cyanoguanidine derivative with the acid derivative carboxylic acid in the presence of an alcohol, consisting in the cyanoguanidine derivative of the general formula 2,

NH

II / ^c x / CN HN ^X N

I. ^H

R

178 167, in which R ¹ is as defined above, is reacted with a carboxylic acid ester of general formula R ³ -COOR ⁴ in which R ^r is as defined above and R ⁴ is Cr-C 6 -alkyl, in the presence of an alcohol of the general formula R-OH, and also in the presence of a base or a carboxylic acid amide selected from the group consisting of N, N-di (C1-C4-alkyl) formamide, N, N-di (C1-C4-alkyl) acetamide and N-methylpyrrolidone and in the presence of a salt of elements such as magnesium, calcium, aluminum, zinc, copper, iron, cobalt, nickel or chromium.

The substituted cyanoguanidine starting material is generally known. N-Methyl or N-ethyl substituted derivatives can be prepared from cyanoguanidine and dialkyl sulfate as described by A.E. Kretov and A.S. Bespalyi in Zuhr. Prik. Khimii, Vol. 34 (1961) pp. 621 et seq. Guanidine can also be used in the form of an acid addition salt, in which case the acid released during the reaction is preferably neutralized by adding a suitable base such as sodium methoxide.

Preference is given to using carboxylic acid esters in which R4 has the same meaning as R2 and R3 is C1-C4-haloalkyl, especially fluoromethyl, chloromethyl, fluoroethyl or chloroethyl, such as CCl3, CF3, CF2CF3, CF2Cl, CFCl2, CH2O, CHCE, CH ₂ F and CHF2. Perhalogenated alkyl groups such as CCl3, CF3 and C2F5 are especially preferred.

According to the invention the reaction of a cyanoguanidine of the formula 2 with an alcohol of formula R ² OH (or R 4 OH, formed by hydrolysis of the ester used of the formula R ^J COOK ^t) is carried out in the presence of a base. Surprisingly, the reactivity of metal chelate complexes can be increased so that reaction with carboxylic acid esters is possible, although these esters are much less reactive than the corresponding carboxylic acid anhydrides or orthoesters.

Suitable bases are inorganic and organic bases. The inorganic bases are preferably alkali metal and alkaline earth metal hydroxides, and the organic bases are tertiary amines such as C1 -C4 trialkylamine, e.g. triethylamine, pyridine or N-methylmorpholine. Preferably, the base is an alkali metal or alkaline earth metal alkoxide of the alcohol of formula R ² OH used in the reaction. This alkoxide can also be prepared in situ, for example, from the appropriate alkali metal or sodium amide or sodium hydride and an alcohol of formula R ^' OH.

Typically, the amount of base is 0.1-2, and especially 0.8-1.2 molar equivalents, based on the cyanoguanidine of formula 2. Larger amounts can be used, but generally do not provide any further advantage.

Instead of a base or additionally, a carboxylic acid amide from the group consisting of N, N-di (C1-C4-alkyl) -formamide, N, N-di (C1-C4-alkyl) acetamide and N-methylpyrrolidone may also be used. By way of example, mention may be made of dimethylformamide, diethylformamide, dimethylacetamide and diethylacetamide. The addition of carboxylic acid amides has proven effective especially when heavy metal salts, especially copper, are used as a chelating agent.

The carboxylic acid amide is usually used in an amount of 1-30, in particular 5-10, molar equivalents based on the cyanoguanidine of formula 2. It may also be advantageous to use the carboxylic acid amide as solvent.

As salts of alkaline earth metals, e.g. aluminum or heavy metals, there are used products which are readily soluble in the reaction medium, such as halides, e.g. fluorides, chlorides or bromides, nitrates, sulphates or phosphates, alcoholates or acetates. The nature of the alkaline earth metal salts is not critical and the appropriate salt is selected for its good solubility and price. Suitable salts are, for example, MgC.l ', Mg (OCH3), CaCl ₂ , Zn (NOs) 2, Cu (CH3COO) 2, AlCl ₃ , AlBr ₃ , ZnCl ₂ , ZnBr ₂ , CuCl ₂ , NiBr ₂ , CrCl ₃ , CaO, Ca (NO ₃ ) ₂ , Mg (NO ₃ ) 2, MgO, ZnO, FeCl2, FeCl ₃ , Fe (NO ₃ ) ₂ , Fe (NO ₃ ) 3. Chlorides are especially preferred, especially CaCl2 and ZnCl2.

An advantage of the process according to the invention is that the use of heavy metal compounds can be largely or completely eliminated, and compounds such as magnesium, especially calcium, can be used instead, which is advantageous for ecological reasons.

178 167

Soluble salts of these elements are particularly preferred. However, very good results are also obtained with the use of zinc compounds.

The salts of the above-mentioned elements may be used in stoichiometric amounts or preferably less than stoichiometric amounts, with respect to the cyanoguanidine of the formula II, e.g. in an amount of 0.001-2 moles, especially 0.005-1, per 1 mole of cyanoguanidine of the formula II.

When heavy metals are used, their amount should be as low as possible, so that only a catalytic amount is used, e.g. less than 0.6 moles per mole of cyanoguanidine. In the case of the magnesium and calcium salts, a particularly preferred amount is 0.01-1.0, especially 0.05-0.5 mol. Of course, an amount greater than the stoichiometric amount, based on the cyanoguanidine of the formula II, can be used, e.g. 1-2 moles per mole of cyanoguanidine, but for economic reasons, amounts below the stoichiometric amounts should rather be used.

The starting alcohol of formula R ² OH may be prepared in situ from a carboxylic acid ester of formula R ³ COOR ⁴ (R ² = R ⁴ ) or added to the reaction mixture (preferably solvent). In the case of using this alcohol as a solvent, it is advisable to select the appropriate alcohol component to form the ester (i.e. r 2 = R ⁴ ) to avoid by-products.

The molar ratio of cyanoguanidine to the alcohol of formula R2OH is generally 1 to 30, especially 5 to 10.

Carboxylic acid ester of the formula R ³ COOR 4 is preferably used in an amount of 0.5-10, in particular 1-5 mol per mole of cyanoguanidine of formula 2 as such esters are especially preferred esters Ct-C4-alkane- or chlorowcoalkanokarboksylowych. such as methyl acetate, ethyl acetate, methyl propionate, ethyl propionate, methyl trifluoroacetate, methyl difluoroacetate, methyl fluoroacetate, methyl trichloroacetate, methyl dichloroacetate, methyl chloroacetate, ethyl trifluoroacetate, methyl or ethyl pentafluoropropionate, and methyl pentachloropropionate, and methyl pentachloropropionate. Due to the specific use of the triazines of the formula I as intermediates in the preparation of crop protection agents, methyl trifluoroacetate and ethyl trifluoroacetate are particularly preferred as starting esters.

The reaction of compounds of formula II with the alcohol of formula R2OH and the ester of formula R3COOR4 can be carried out using only these substances, i.e. without addition of inert solvents. ROH alcohol is preferably used simultaneously as the solvent. According to a particularly preferred embodiment, an appropriate alcoholate is then selected as the base.

The reaction is carried out at a temperature of 0-200 ° C, preferably 20-150 ° C, and in particular at the reflux temperature of the reaction mixture.

Special pressure conditions are not required and the reaction is usually carried out at atmospheric pressure or under the natural pressure of the reaction medium in question.

The reaction can be carried out continuously or batchwise. In the case of a continuous operation, the reactants are preferably passed through a tubular reactor or a cascade of tubular reactors.

According to a particularly preferred process according to the invention, the triazine of the formula I is prepared without isolating the intermediates; for example by placing a cyanoguanidine of formula 2, an ester of formula R3COOR4 and a less than stoichiometric amount of an alkaline earth metal salt or metal salt in the alcohol R2OH as solvent, dosing a base, e.g. an alkali metal alkoxide such as NaOR2 or KOR2, and the mixture heated to reflux.

The reaction is usually terminated in a known manner when no cyanoguanidine can be detected in the reaction mixture (e.g. by thin layer chromatography, high performance liquid chromatography or gas chromatography).

Subsequently, work-up is usually carried out by known methods, e.g. by distillation, filtration, centrifugation or by addition of water followed by extraction, to obtain the reaction product of the formula I.

The products obtained can optionally be further purified, for example by crystallization, rectification or chromatographic methods.

178 167

The triazines of formula I prepared by the simple process of the invention are valuable intermediates for the synthesis of dyes, medicaments and plant protection agents, in particular herbicides, such as those described, for example, in EP-A 508 348, EP-A 111 442 or DE- A 40 38 430.

The following examples illustrate the invention.

Example I. Preparation of 2-atininO-4-methoxyT) 4-riffuoTomethyl-1,3,5-triazine.

To 400 ml of methanol were added 21 g (0.25 mol) N-cyanoguanidine, 3.4 g (0.025 mol) of anhydrous zinc chloride and 160 g (1.25 mol) of methyl trifluoroacetate. The mixture was heated to 50 ° C and 50 g (0.27 mol) of a 30% solution of sodium methanol was pumped in 10 hours. The solvent was then largely removed, the residue washed with 250 ml of water and 250 ml of dilute hydrochloric acid and dried at 60 ° C / 2 kPa. 43.2 g (0.22 mol, 89%) of 2-amino-4-methoxy-6-trifluoromethyl-1,3,5-triazine were obtained in the form of a colorless powder (HPLC:> 99% by weight). Melting point: 161-163.5 ° C.

Example II. Preparation of 2-amino-4-methoxy-6-trifluoromelyl-1,3,5-triazine.

56.6 g (0.5 mol) of calcium chloride (98%, powdered) and 210 g (2.5 mol) of N-cyanoguanidine were added to 2 liters of methanol. The mixture was heated with stirring to reflux for 1 hour and a homogeneous solution was obtained. The mixture was then cooled to. at room temperature and 640 g (5.0 mol) of methyl trifluoroacetate was added, then 450 g (2.5 mol) of a sodium methanol solution (30% by weight in methanol) over 2 S minutes, with the formation of a white precipitate. After heating for 2 hours at reflux, the mixture was cooled to room temperature and the pH was adjusted to about 6 by addition of concentrated hydrochloric acid. Then methanol was distilled off, about 2 liters of water were gradually added, and the precipitated white crystalline crystals were separated and dried in vacuo. 402.4 g of product are obtained (2.07 mol; 83% of theory).

1 H-NMR spectrum (270 MHz), CDCl ₃ , int TMS, δ (ppm)): 6.45 br (1H); 5.88 br (1H); 4.03 s (3H).

Example ΠΙ. Preparation of 2-amino-4-methoxy-6-trifluoromethyl-1,3,5-triazine.

Dr 600 ml of methanol was added 84 g (1 mol) cyjoio ^ iainidyny and l00 ^l '- ^1,3 intriguing), copper acetate and i6 ^ n ^^ ^e iesmnm wedn 7 it TEM ^t em ^g ęraturpn wnenia in wanenkach reflux. ^{at a} time up to 20 ° C total pressure (sire ^a ltnono jwozl poor pressure mrm ^- constant mtadrn ⁽ higher pedal with changed c ^l m ⁾ o ^ o. The residue in the amount of 41.4 g ^, 1 mol) dissipated in 200 ml methanes ^and harvest within 15 Minot wtaoplono ^axis 5 ^1.4 g of 4 mol) ^c 0% roztwowu metanotanu so ^(u. Noaiępn ^e wYkiOptono 7 ^(s g (0.6 mol) of methyl trifuorooctpcu and the mixture for 2 ygw8wnyo h tempyta ^and nrze ccrzorua in warunkan ^y .owaotu nkrppliin. M.eszynłn ⁰ oah.oitaono dg toilet. odpąnzano aoyowonofiole ^C oc ^p nubsaan Otal (28, g and ^y. M ^ ^s wife Łu myoieyoysty. MzCStotato prnenwlo interior and ^Y a wysyioąssu . Otrnymana 1 6AG 5 ° C, ⁰ zamżta, 38%) from N, N-cyano) tsiozyr ^ ^y.

P) ⁰ with ^y aza ^iP0 Wytwarzani5 Mnmnto-C metaksytostrifhtorzmetylo-l, 3,5-triazine.

^P o 3 ^y 0 nd D M'F s ° daoo 4 ^a , 4g 20, Ί moh) copper taempleks n at Wadu ΙΠ ^p in c. 15 winnt wkroplyoo at 20 ^O C 51.2 g (0.4 mol) the butterfly trifnorooctann. After that, I am ggrcewnno by ^s gndzrnC in 5 OM and 5 hours in MC. Nietaesk ¹ toziwó on reakayjny oatezona and ^p ozostałg ^E C zmis.czanoC.s loom. according to ^{yd 1} 1 00 threshed salt kovar. After pozeeeąazeΩ ^l oawiesmy pyai emnigjszonym d ^ meniem, p-zemY-crn ρι.Ε, ι ΓΡΕηουΟι ^ ο and wysuozeniu knots ¹ o ^s ki otteymlwo MA g (, 1 ^ mota). 6 0%) Welcome laiazyoy ra posUKe bnn ^p rnnnnngę ^p eosdta.

Ex V. Wytwarzanie2 ^{y-amino-4-methoxy-6-trifluoromethyl-l,} 3,5-triazine.

^P 4 ^P g 8.4 g etenota tatakoo 204 mol) and MA nylanogu6nidyny g (0.2 ⁵ r ^ i ^ <^ t toifluorooctaeu all ety.u ^p e dague ⁰⁰ minutes Mwe zawtaamę 8, ⁿ g ^p .l25 η ^ Ει) 2 tscokine of sodium in 3 ^y , ⁰ g of ethanol u. ^N o ^ą g ^u amu 50 ⁰ g (Ό, ³⁰ motaj of calcium nneiDan.ine renkcyin ngreewago panez 7 hours in this ^ eratra in the period ^{0 p} osv , Oln nloajihn. In 20 ⁽ 'C ⁿ o stano 0.5 from styrn.ne.p salt quar. Seontono atanaLPo ⁿ o ^k oo ^t u 10 ^N g rnYody nawroCi.ro ^d azes ^ρ ο5οηο momentum nnuncjscnr ^ ym nińneoiem. Remain. ^ o 50 m ^g co ^{dp l} n ^w suinane in tem ^e seu ^o f l3nu 5 ⁿⁿ C / 2 kPa. Ota ^ mn ^ o 1 8.6 ^z scpOSO mota, ^0p %) 2-nmino48

178-167 methoxy-6-trifluoromethyl-1,3,5-triazine as a colorless powder (HPLC: 99.8, F1-%; mp 124-125 ° C).

Example VI. Preparation of 2-amino-4-methoxy-6-difluoromethyl-1,3,5-triazine. A solution of 1.9 g (23 mmol) of N-cyanoguanidine and 2.6 g (23 mmol) of calcium chloride in 50 ml of methanol was stirred for 90 minutes under reflux. The reaction mixture was cooled to 20-25 ° C and 5.0 g (45 mmol) of methyl difluoroacetate was quickly added dropwise followed by the slow dropwise addition of 4.1 g (23 mmol) of sodium methoxide solution (30% by weight in methanol), with white separation. precipitate. After stirring for 2 hours at reflux, the volatiles were removed under vacuum with a water pump and at a bath temperature of 40 ° C. The residue was then partitioned between 100 ml of water and 100 ml of ethyl acetate, and the organic phase was separated and dried over MgSO4. Removal of the solvent at 40 ° C under reduced pressure with a water pump afforded the title compound as a slightly impure oil (1.1 g, 6.3 mmol; 28% of theory) which could be made crystalline by trituration if necessary. with ether / hexane (1: 3 by volume).

1 H-NMR spectrum (400 MHz, CDCl ₃ , int. TMS, δ (ppm): 7.44 br (1H); 6.97 br (1H); 6.27 t (2Jhf = 55Hz, 1H); 3 , 96s (3H).

¹³ C-NMR spectrum (100 MHz, CDCl 3 / CD 3 S (O) CD 3, int. TMS, δ (ppm), proton decoupling): 171.5 s (C-OCH 3); 169.8 t _(C-CHF2, 2 J _CF = 25 Hz); 168.8 s (C-NH2); 11.3 t (CHF2, 1c-f = 243Hz); 54.7 s (OCH3).

Publishing Department of the UP RP. Circulation of 70 copies

Price PLN 2.00.

Claims (13)

Patent claims 1. Process for the preparation of triazine derivatives of general formula 1 HN R N OR 1 0 Λ where R is hydrogen, methyl or ethyl, R is C 1 -C 4 -alkyl) and R is C 1 -C 4 -alkyl optionally substituted with one or more chlorine or fluorine atoms by reacting the cyanoguanidine derivative with the carboxylic acid derivative in the presence of an alcohol characterized in that the cyanoguanidine derivative of the general formula 2, NH C _{x X} CN HN ^X N> and ^H R in which R 1 is as defined above, are reacted with a carboxylic acid ester of the general formula R ³ -COOR 4 in which R ^r is as defined above and R ⁴ is C 1 -C 4 -alkyl, in the presence of an alcohol of the general formula R ² -OH, and also in the presence of a base or a carboxylic acid amide selected from the group consisting of N, N-di (C 1 -C 4 -alkyl) formamide, N, N-di (C 1 -C 4 -alkyl) acetamide and N-methylpyrrolidone and in the presence of salts of elements such as magnesium, calcium, aluminum, zinc, copper, iron, cobalt, nickel or chromium. 2. The method according to p. The process of claim 1, wherein the base is an alkoxide or a tertiary amine. 3. The method according to p. 1, characterized in that the base is an alkali metal alkoxide or alkaline earth metal and an alcohol of formula R ² -OH. 4. The method according to p. The process of claim 1, wherein the salt is a halide, nitrate, sulfate, alkoxide or acetate. 5. The method according to p. The process of claim 1, wherein the salt is used in an amount of 0.001-2 moles per mole of cyanoguanidine of the formula 2. 6. The method according to p. The method of claim 1, wherein the heavy metal salt is used in an amount less than the stoichiometric amount with respect to the cyanoguanidine of formula 2. 7. The method according to p. The process of claim 1, wherein the alkaline earth metal salt is a calcium or magnesium salt. 8. The method according to p. The process of claim 7, wherein the alkaline earth metal salt is used in an amount of 0.001-2 moles per mole of cyanoguanidine of the formula 2. 9. The method according to p. The process of claim 1, wherein the carboxylic acid ester is a C1-C4 alkyl ester of a perfluorinated or perchlorinated C1-C3 carboxylic acid. 178 167 10. The method according to p. The process of claim 1, wherein methyl trifluoroacetate is used in methanol in the presence of an alkali metal methanol as a base. 11. The method according to p. The process of claim 1, wherein methyl trifluoroacetate is reacted with cyanoguanidimio of formula 2 in the presence of alkali metal methanol and calcium salt. 12. The method according to p. The process of claim 1, wherein methyl trifluoroacetate is reacted with cyanoguanidine of formula II in N, N-dimethylformamide in the presence of a copper salt. 13. The method according to p. The process of claim 1, wherein methyl trifluoroacetate is reacted with a cyanoguanidine of formula 2 in the presence of an alkali metal methoxide and a zinc salt.